SND1 acts as an anti-apoptotic factor via regulating the expression of lncRNA UCA1 in hepatocellular carcinoma
SND1 acts as an anti-apoptotic factor via regulating the expression of lncRNA UCA1 in hepatocellular carcinoma
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SND1 通过调节肝细胞癌中 lncRNA UCA1 的表达发挥抗凋亡因子的作用。
DOI：
10.1080/15476286.2018.1534525
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发表时间：
2018-01-01
期刊：
影响因子：
4.1
通讯作者：
Yang, Jie
中科院分区：
文献类型：
--
作者：
Cui, Xiaoteng;Zhao, Chunyan;Yang, Jie
多功能的SND1(葡萄球菌核酸酶和Tudor结构域包含1)蛋白被认为与不同类型的RNA分子有关，包括mRNA、miRNA、Pre-miRNA和dsRNA。SND1参与了真核细胞的许多生物学过程，包括细胞周期、DNA损伤修复、增殖和凋亡。然而，关于SND1在哺乳动物细胞中的抗凋亡作用的具体分子机制在很大程度上仍然不清楚。在这项研究中，通过对在线HPA(人类蛋白质图谱)和TCGA(癌症基因组图谱)数据库的分析，发现SND1在肝癌患者中显著高表达。我们发现，在肝癌化疗药物5-FU(5-FU)刺激下，SND1的下调或完全耗竭可增强肝癌细胞的凋亡水平。SND1通过调节尿路上皮癌相关基因1(UCA1)的表达来影响5-FU诱导的肝癌细胞的凋亡水平。此外，MYB(MYB原癌基因，转录因子)可能参与了SND1在UCA1表达的调控。综上所述，本研究通过对LncRNA UCA1的调控，证实了SND1是肝癌细胞中的一种抗凋亡因子，为揭示SND1蛋白与LncRNA之间的关系提供了新的思路。
Multifunctional SND1 (staphylococcal nuclease and tudor domain containing 1) protein is reportedly associated with different types of RNA molecules, including mRNA, miRNA, pre-miRNA, and dsRNA. SND1 has been implicated in a number of biological processes in eukaryotic cells, including cell cycle, DNA damage repair, proliferation, and apoptosis. However, the specific molecular mechanism regarding the anti-apoptotic role of SND1 in mammalian cells remains largely elusive. In this study, the analysis of the online HPA (human protein atlas) and TCGA (the cancer genome atlas) databases showed the significantly high expression of SND1 in liver cancer patients. We found that the downregulation or complete depletion of SND1 enhanced the apoptosis levels of HepG2 and SMMC-7721 cells upon stimulation with 5-Fu (5-fluorouracil), a chemotherapeutic drug for HCC (hepatocellular carcinoma). SND1 affected the 5-Fu-induced apoptosis levels of HCC cells by modulating the expression of UCA1 (urothelial cancer associated 1), which is a lncRNA (long non-coding RNA). Moreover, MYB (MYB proto-oncogene, transcription factor) may be involved in the regulation of SND1 in UCA1 expression. In summary, our study identified SND1 as an anti-apoptotic factor in hepatocellular carcinoma cells via the modulation of lncRNA UCA1, which sheds new light on the relationship between SND1 protein and lncRNA.